Chronic myeloid leukaemia (CML) has a worldwide incidence of 1 to 2 per 100 000 of the population. Most cases are caused by translocation of the distal end of chromosome 9 on to chromosome 22 which leads to the creation of a fusion protein expressed from the fusion gene formed by juxtaposition of parts of the BCR and ABL1 genes. The resulting oncoprotein is a constitutive tyrosine kinase and appears to operate as an initiator for the development of the leukaemia. Clinical features—many patients are asymptomatic at diagnosis, which is made following a routine blood test. Others present with signs and symptoms including fatigue, sweats, fever, weight loss, haemorrhagic manifestations, and abdominal discomfort (due to splenomegaly). Diagnosis—this is typically made by the examination of a peripheral blood film and the demonstration of the Ph chromosome by conventional cytogenetics in a bone marrow aspirate or peripheral blood sample. Polymerase chain reaction analysis of peripheral blood confirms the presence of a BCR-ABL1 transcript and characterizes the BCR-ABL1 junction. Treatment—the original TKI, imatinib, has had a very significant impact on the first-line management of patients with CML. It induces durable complete cytogenetic responses in the majority of patients and prolongs overall survival substantially. Second- and third-generation TKIs show enhanced potency against BCR-ABL1 activity and are licensed within Europe for first-line (dasatinib, nilotinib) or second-line or subsequent (dasatinib, nilotinib, bosutinib, ponatinib) use in CML. Patients with suboptimal responses to first-line treatment can be offered a different second-line TKI; or a third-line TKI, such as ponatinib; or allogeneic stem cell transplantation—for patients less than 65 years of age and with a suitable donor.
Successful peripheral blood stem cell mobilisation with filgrastim in patients with chronic myeloid leukaemia achieving complete cytogenetic response with imatinib, without increasing disease burden as measured by quantitative real-time PCR